Growth Differentiation Factor 15: A Prognostic Marker in Patients with Acute Chest Pain without Acute Myocardial Infarction.

BACKGROUND: Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI. METHODS: In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF). RESULTS: Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69-4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31-10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11-6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality. CONCLUSIONS: Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events.

A case report of giant cell myocarditis complicated by severe heart failure: the value of early endomyocardial biopsy and mechanical circulatory support.

Background: Giant cell myocarditis (GCM) is a rare, probably underdiagnosed and potentially fatal disease in young and middle-aged patients. Disease progression is often rapid, and life-threatening arrhythmias and cardiogenic shock due to progressive left ventricular failure are among the most feared complications. Although cardiac biomarkers and multimodality imaging are used as initial diagnostic tests in most patients, endomyocardial biopsy (EMB) is often required for a definitive diagnosis. However, there are still gaps in our knowledge in terms of the etiology, early diagnosis, management and prognosis of GCM. Case Description: We present the case of a male patient in his early 50s admitted to Haukeland University Hospital with fulminant GCM. He had no significant medical history in the past apart from hypertension, and presented to hospital in cardiogenic shock after a few weeks of progressive shortness of breath. Rapid initiation of methylprednisolone had an immediate effect on reducing myocardial inflammation, and sustained treatment with a combination of immunosuppressive agents along with optimal heart failure medications led to complete recovery of the heart function and clinical remission over several years. The case study highlights the urgency of an early EMB, access to mechanical circulatory support (MCS) and the efficacy of immunosuppressive treatment and optimal medical management for heart failure. Finally, our review of the literature also provides an updated guidance on the contemporary management of GCM patients. Conclusions: Accurate and early diagnosis with EMB in patients with GCM are crucial for better outcomes. Rapid initiation of methylprednisolone reduces myocardial inflammation and the risk of death. Sustained treatment with a combination of immunosuppressive agents together with optimal heart failure medications are essential for myocardial recovery and long-term stabilization. The use of MCS is the cornerstone in the management of GCM with a clear survival benefit.

An Unexpected Cause of Severe Hypertension and Bradycardia: The Role of Hemodynamic Assessment by Echocardiography.

Severe hypertension has numerous etiologies. When accompanied by bradycardia, the spectrum of differential diagnoses is greatly narrowed and is commonly seen in patients with increased intracranial pressure. However, other etiologies such as bradycardia-induced hypertension are rarely mentioned. Here we report the case of a 73-year-old woman presenting with symptoms of heart failure, severe hypertension, and bradycardia with a 2:1 atrioventricular block. Echocardiography demonstrated increased left ventricular filling secondary to bradycardia and prolonged diastole, leading to greater ventricular stretch, increased contractile force and greater stroke volume (Frank-Starling mechanism), which subsequently caused elevated systolic blood pressure (BP), low diastolic BP and a wide pulse pressure. Treating the bradycardia by pacing led to an immediate and substantial BP reduction, although complete BP normalization had a slower time course and was probably due to the concomitant effect of the antihypertensive treatment initiation. This pathophysiological mechanism has received little attention in the literature. Further, stimulation of sympathetic afferents located in the heart by distension of the cardiac walls as well as the role of vagally innervated cardiopulmonary receptors due to the increased pressure in the heart and the pulmonary artery should also be kept in mind as alternative hypotheses.

Experimental evaluation of a commercial footrot vaccine against native Canadian strains of Dichelobacter nodosus.

Two serotypes of the anaerobic bacterium Dichelobacter nodosus were used to experimentally infect young sheep resulting in infectious pododermatitis or footrot characteristic of the natural disease in sheep. The specific serotypes of D. nodosus were reisolated from the feet and identified using immunofluorescent microscopy of hoof scrapings. Prior immunization of sheep with a commercially available bacterin containing whole cell preparations of ten strains of D. nodosus resulted in serum IgG reactive to a serotype of D. nodosus common to the vaccine. Immunization also produced serum IgG reactive to a serotype of D. nodosus not incorporated in the vaccine. A less severe infection occurred in the immunized sheep than in the controls regardless of the serotype of bacteria used to infect them. Clinical lameness and lesion severity were milder in sheep infected with the serotype of D. nodosus common to the vaccine. Western blot analysis of sera from convalescent sheep showed cross-reactive antibodies to nonfimbrial cell surface proteins, as well as bacterial lipopolysaccharide. Such cross-reactivity may explain the partial protection seen in animals infected with a serotype distinctive from the ones in the vaccine. Despite the historical emphasis of fimbrial immunogens in ovine footrot this study using a new model of experimental ovine footrot suggests other surface antigens may also be important in protective immunity.

Serological classification and virulence determination of Dichelobacter nodosus isolated from Alberta and British Columbia sheep.

Ovine footrot is a contagious disease of sheep that occurs in temperature climates. It is caused by the strict anaerobe, Dichelobacter nodosus. Benign and virulent organisms are differentiated according to serotype and protease production. This study was conducted to identify the presence of virulent serotypes of D. nodosus in sheep flocks in Alberta and British Columbia. Dichelobacter nodosus was detected in lame sheep from 11 of 15 (73%) flocks in Alberta and in 4 of 5 (80%) British Columbia flocks. It was recovered from 57 of 107 (53%) lame sheep. In Alberta, 4 distinct serotypes were isolated from the 11 positive flocks while in British Columbia a total of 6 different serotypes were isolated. One British Columbia isolate could not be classified into existing serotypes. Of the 19 field strains tested, all but 3 were defined as virulent based upon the rapid rise in protease activity in vitro which was maintained between 3 and 5 d. The knowledge of the serotype and virulence of the D. nodosus isolated from affected animals can assist in the control and prevention of ovine footrot.

Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals received either: 1) Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg tilmicosin per kg body weight (n = 12). Calves that were non-infected and tilmicosin-treated were also included for determining tilmicosin concentrations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and 72 h (n = 3-per time). In the infected calves, response to therapy was monitored clinically. Serum samples were collected for determination of tilmicosin concentrations using HPLC. Any animal becoming seriously ill was humanely killed. Complete necropsy examinations were performed on all animals and included gross pathologic changes, bacteriologic analysis, histopathology, and determination of pulmonary concentrations of tilmicosin. Tilmicosin treated animals responded significantly better to therapy than saline-treated control calves. Clinical assessment of calves during the study indicated that tilmicosin-treated calves had significantly improved by T = 8 h compared to satine-treated animals (P < 0.05). At necropsy tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while of the tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica. Mean (+/- standard error) serum tilmicosin concentrations in infected calves peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P. haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to serum concentrations of tilmicosin in non-infected tilmicosin-treated calves. Lung tissue concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight.